Why Do Autoimmune Diseases in Women Seem More Common Than in Men?

Key Points

• Autoimmune diseases affect more women than men.
• The exact cause is unknown, but it could be due to a number of factors.
• Anything from the X chromosome to genes to nail polish may determine the difference.

Women are at a greater risk of having an autoimmune disease than men—four times greater, in fact—and at least 85 percent of autoimmune disease patients are female.

"Almost all of the main rheumatologic diseases, such as lupus, rheumatoid arthritis, Sjogren's syndrome and so forth, are more common in women," said Jason Liebowitz, M.D., a rheumatologist and assistant professor of medicine at Columbia University Irving Medical Center in New York City.

One of the most significant questions is, "Why?"

What causes autoimmune diseases?

Autoimmune diseases are characterized by an inflammatory response to the body's tissue, resulting in tissue damage by antibodies and T-cells.

The risk of autoimmune disease is determined by a combination of genes, the immune system and environmental factors. Genes determine how susceptible someone is to autoimmune diseases, although environmental factors may trigger an autoimmune disease.

The immune system contributes to this if it is dysregulated.

"For example, in patients with celiac disease, alternatively termed sprue or gluten-sensitive enteropathy, a particular set of inherited genetic markers are almost universally seen," said Elliot Rosenstein, M.D., director of the Institute for Rheumatic & Autoimmune Diseases at Overlook Medical Center in Summit, New Jersey. "Yet, the condition only develops when the predisposed individual has consumed gluten, a protein found in wheat, barley and rye."

This is the environmental trigger.

The role of hormones, the X chromosome and pregnancy

If genes, the immune system and the environment affect autoimmune diseases in everyone, why does autoimmunity disproportionately affect women?

"We are not sure," Liebowitz said. "But some hypotheses include the different effects of sex hormones between men and women, the effect of what is called X chromosome inactivation, and differences in gut microbiome populations between men and women."

X chromosome inactivation is a protective measure that occurs in female mammals during embryonic development to reduce the risk of detrimental X-linked genes. It happens when one of the X chromosomes in a woman's genetic makeup is compacted, making many of those genes inactive.

"X inactivation is not complete, and 15 to 20 percent of genes from the inactive X chromosome escape the process and can be expressed," Liebowitz said.

You may not be able to avoid developing an autoimmune condition, but you can minimize your risk.

This means women have a more mosaic gene expression than men, or multiple expressions of one gene. This creates a higher chance of expressing the genes linked to autoimmune disease, and it means that women express more genes that code for inflammatory responses than men do.

Another potential contributor to a higher autoimmune incidence in women is the increased antibody production that happens during pregnancy. Fetuses depend on antibodies provided to them in the womb to withstand the assault of pathogens they face after birth.

The theory is that this uptick in antibody production may cause autoimmune flare-ups in women during pregnancy or the postpartum period, but there isn't enough agreeing evidence to say with certainty that pregnancy affects autoimmune risk.

"In general, women are believed to have more robust immune responses," Rosenstein said. "Estrogen may contribute to this, whereas androgens tend to inhibit these reactions."

This is an oversimplification, however, Rosenstein said, and the complex nature of autoimmune disorders in women is evident in the sheer variety of them. Lupus is worse in the childbearing years, and this may be linked to estrogen, but Sjogren's syndrome worsens after menopause. Prolactin, a hormone that helps breast development and milk production in pregnancy and after birth, may contribute to autoimmunity.

Apart from biology, women may be disproportionately affected by autoimmune disease because of inflammatory cosmetics they are more exposed to in their environment, such as hair dye, lipstick and nail polish.

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Autoimmune diseases in men

While most rheumatologic diseases are more common in women, there are a few that disproportionately affect men, including the following:

• Ankylosing spondylitis, a condition in which some of the spinal vertebrae fuse
• Guillain-Barré syndrome (particularly in older patients), a condition that affects the nerves
• Reactive arthritis, joint inflammation triggered by infection elsewhere in the body
• Psoriatic arthritis, joint inflammation that affects some people who have psoriasis

While these disorders are associated more with men, it may reflect bias in specialists' ability to ascertain diagnoses rather than a truly higher incidence in men, Rosenstein said.

Can you prevent autoimmune disorders?

You may not be able to avoid developing an autoimmune condition, but you can minimize your risk. How? Don't smoke, avoid or reverse obesity, get regular exercise and eat a nutritious diet. They all can help.

Foods from the Mediterranean diet in particular, such as fatty fish, can mitigate the risk of developing rheumatoid arthritis, lupus and related conditions.

"Diet seems to play a significant role," Liebowitz said. "Consumption of adequate vitamin D also appears to have some protective effects."

Avoiding autoimmune disease may be impossible, so it's important to know the symptoms. If you experience unexplained joint pain with stiffness and swelling in the morning, you should seek medical help—especially if this is accompanied by symptoms such as weight loss, fever, rashes, ulcers in the nose or mouth, a dry mouth, and exceptionally dry eyes.

The bottom line

The reason autoimmune diseases affect more women than men is unknown. It could be down to the X chromosome, hormones, the gut microbiome or even nail polish—or the result of multiple factors.

Autoimmunity isn't avoidable, but a nutritious diet, regular exercise and keeping away from tobacco give you the best chance at living a healthy life with an autoimmune disease.